Temazepam

Oral🕒 Plan

Route dataPsychonautWiki

🧬 Receptor activityPHDC

Mechanism of actionPH

Gamma-Aminobutyric acid (GABA) is considered the principal inhibitory neurotransmitter in the human body. When GABA binds to GABA(a) receptors found in neuron synapses, chloride ions are conducted across neuron cell membranes via an ion channel in the receptors. With enough chloride ions conducted, the local, associated neuron membrane potentials are hyperpolarized - making it more difficult or less likely for action potentials to fire, ultimately resulting in less excitation of the neurons. Subsequently, benzodiazepines like temazepam can bind to benzodiazepine receptors that are components of various varieties of GABA(a) receptors. This binding acts to enhance the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells. Combined with the notion that such benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action.

PharmacodynamicsPH

Temazepam is a benzodiazepine used as a hypnotic agent in the management of insomnia. Temazepam produces CNS depression at limbic, thalamic, and hypothalamic levels of the CNS. Temazepam increases the affinity of the neurotransmitter gamma-aminobutyric acid (GABA) for GABA receptors by binding to benzodiazepine receptors. Results are sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action. In sleep laboratory studies, the effect of temazepam was compared to placebo during a two week period. The studies demonstrated a linear dose-response improvement in total sleep time and sleep latency with substantial drug-placebo differences apparent for total sleep time and for sleep latency at higher doses of temazepam. Regardless, REM sleep was ultimately unchanged but slow wave sleep was decreased. Moreover, a transient syndrome, known as "rebound insomnia", wherein the symptoms that led to treatment with temazepam in the first place recur in an enhanced form, may happen on withdrawal of temazepam treatment. The possibility of this occurrence is in part why long term use of temazepam is not recommended due to worries over tolerance and dependence wherein patients' bodies become physiologically accustomed to the regular presence and pharmacological effect of higher and higher doses of the benzodiazepine used. The duration of hypnotic effect and the profile of unwanted adverse effects may be influenced by the distribution and elimination half-lives of the administered temazepam and any active metabolites that may be formed. When such half-lives are long, the drug or its metabolite(s) may accumulate during periods of nightly administration and be associated with impairments of cognitive and motor performance during waking hours. Conversely, if half-lives are short, the drug and metabolites would be cleared before the next dose is ingested, and carry-over effects related to sedation or CNS depression should be minimal or not present at all. However, during nightly use and for an extended period, pharmacodynamic tolerance or adaptation to some effects of benzodiazepine hypnotics may develop - which may also contribute to the possibility of 'rebound insomnia'. Consequently, if the drug has a very short elimination half-life, it is possible that a relative deficiency (for example, in relation to benzodiazepine GABA(a) receptor sites) may occur at some point in the interval between each night's use. This sequence of events may account for certain clinical findings reported happening after several weeks of nightly use of rapidly eliminated benzodiazepine hypnotics, including increased wakefulness during the last third of the night and the appearance of increased daytime anxiety.

Pharmacokinetics

External links